L11

Question 1

Which receptors are responsible for T cell adhesion?

Answer 1

LFA on T cell - ICAM on APC
- Integrins
CD4 a little

Question 2

What receptors are responsible for T cell signal transduction?

Answer 2

CD3 & weird squiggly receptors with ITAM

Some CD4

Question 3

What is the concept of inside-out signaling for T cells?

Answer 3

Chemokine or TCR binding
- Create conformation change - ↑integrin receptor affinity
- Cluster integrin receptors around TCRs
NET: stronger adhesion of APC & T cell –> stronger TCR signaling

Question 4

What cytokine is important for T cell costimulation?

Answer 4

IL2 - T cell differentiation and proliferation
Signal 1 + 2 = T cell activation
IL2 production AND
+ alpha subunit to IL2-R -> high affinity receptor –> respond stronger to IL2 produced

Question 5

Which receptors are inhibitory of T cells?

Answer 5

T cell - APC
PD 1 - PD
CTLA4 - B7

Question 6

Where do you usually find CTLA4 receptors in a resting T cell? What happens when T cell activated?

Answer 6

Inside cell in vesicles 
T cell activation:
- Move to surface
- Interact with B7 with higher affinity
- Recruits ITIMs

Question 7

What are T cell microclusters?

Answer 7

The idea that TCRs can’t signal transduce

Instead, they recruit all needed molecules into a cluster underneath

Question 8

Explain TCR signal transduction.

Answer 8

TCR binds
Lck +P to ITAMs on CD3 & weird squiggly
Recruits ZAP70

Question 9

What are the 3 goal TFs of the TCR signaling cascade? What is their communal function?

Answer 9

NA-FT
NFkB
AP1
All ↑ IL 2 for T cell differentiation and proliferation

Question 10

How do T cells make NA-FT?

Answer 10

Lck
ZAP 70
IP3
↑[Ca2+]
Calcineurin

Question 11

How do T cells make NFkB?

Answer 11

Lck
ZAP 70
PKC
NFkB

Question 12

How do T cells make AP1?

Answer 12

Lck
ZAP70
RAS signaling 
MAP kinase 
AP1

Question 13

What is methotrexate?

Answer 13

Drug that blocks T cell replication

Question 14

What is belatacept?

Answer 14

Drug blocks signal 2: B7-CD28

No T cell development

Question 15

What is cyclosporin? What is the genetic variant for metabolism?

Answer 15

Inactivates calcineurin

CYP3A5

Question 16

What is basiliximab?

Answer 16

Ab against IL2-R

No clonal expansion of T cells

Question 17

What is sirolimus?

Answer 17

Blocks IL2-R signaling

Question 18

What chemokine receptor directs cells into the B zone of lymph nodes? T zone?

Answer 18

B zone: CXCR5

T zone: CCR7

Question 19

What chemokine directs T cells out of the lymph node into the blood?

Answer 19

S1P

Question 20

What chemokine directs T cells out of the blood and into specific tissues?

Answer 20

CXCR3

Question 21

What is the fxn of drug FTY720?

Answer 21

Blocks S1P receptor

T cells stay in lymph node

Question 22

In general, tyrosine phosphatases work to decrease tyrosine kinase activity in T cell inactivation. What happens if you have mutations in your phosphatases?

Answer 22

Inability to regulate immune responses:
Cancer - too much T cell dampening
Autoimmunity - too little

Question 23

What is activation induced cell death?

Answer 23

Negative regulation of T cells
FasL expressed on T cells after activation
FasL + Fas (receptor on neighboring T cells)
- Fas = TNF death receptor, works via caspases
Fas trimerizes
DNA fragmentation

Question 24

What is human autoimmune lymphoproliferative syndrome (ALPS)?

Answer 24

Mutation in Fas

No activation induced cell death of T cells

Question 25

What is CD95?

Answer 25

Fas receptor on T cells

Question 26

What is necessary for BCR activation?

Answer 26

Cross linking!!!

Question 27

Explain BCR signaling. What are the downstream products?

Answer 27

Cross link BCRs & bind TAAPA
Blk, Fyn, or Lyn +P to ITAMs on CD19 & Ig alpha/beta
SYK
Downstream products: NF-AT, NFkB, AP1

Question 28

What is the negative regulation for B cells?

Answer 28

Ab Fc region binds BCR instead of antigen

Enacts ITIM